Mild [Pd(OAc)2/PPh3] catalyzed cyclization reactions of N-Alkyl-2-vinylazetidines with heterocumulenes.

Abstract

A synthetic route to N-alkylated 2-vinylazetidines is presented, and highly regioselective methods for the palladium(0)-catalyzed insertion of heterocumulenes into these substrates have been established, employing a Pd(OAc)2/PPh3 catalyst system under very mild conditions. An assortment of tetrahydro-pyrimidin-2-ones, tetrahydro-pyrimidin-2-imines, and [1,3]thiazinan-2-imines have been acquired in reactions with isocyanates, diarylcarbodiimides, and arylisothiocyanates. Unoptimized results in reactions with ketenes and ketenimines indicate a variety of carbon electrophiles could be used for the insertion and suggest great potential for these methods in organic synthesis. The steric and electronic influence of substituents on either the azetidine or carbodiimide has established maximal characteristics of substrates suitable for the insertion. Two conformational isomers result from insertion of o-tolylisocyanate into a variety of 2-vinylazetidines, indicating that enhanced congestion about the heterocycle creates an energy barrier at room temperature and inhibits ring flexibility. Stereochemical and regiochemical evidence support a likely catalytic cycle that involves the formation of a pi-allylpalladium intermediate as the active species for insertion and an equilibrium between a kinetic and thermodynamic product. An asymmetric procedure for the synthesis of optically active products could not be established, which suggests a more complex catalytic cycle.